P1416: THE CLINICAL SPECTRUM AND PROGNOSTIC FACTORS OF ERDHEIM-CHESTER DISEASE
Authors: Jia-Wen Dai, Xin-Xin Cao, Jian LI, Dao-Bin Zhou, Long Chang, He Lin
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Erdheim-Chester disease (ECD) are rare and fatal histiocytoses. Due to the rarity, the difficulty of diagnosis, little information exists on the long-term outcome of treatments Aims: The aim of this retrospective study was to describe the clinical manifestations, genetic analysis, treatment, outcome, and prognostic factors of ECD and mixed Langerhans cell histiocytosis (LCH) and ECD patients. Methods: A total of 75 ECD patients and 10 mixed LCH and ECD patients in Peking Union Medical College Hospital were enrolled in this study. We analyzed the clinical manifestations, genetic analysis, treatment, outcome, and prognostic factors of these patients. Results: Among the 85 patients, 42 were males and 43 were females. The median age at diagnosis in ECD patients was older than patients with mixed LCH and ECD (46 years old vs 31 years old, P=0.006). Four ECD patients were younger than 18 years old. One patient had cooccurrence of acute myeloid leukemia (AML).The median time from symptom onset to diagnosis was 31 months. The median number of organs involved was 5.5, among which bones (96.0%), lungs (64.0%), central nervous system (CNS) (54.7%), retroperitoneum (52.0%), blood vessels (52.0%), heart (48%), pleura (45.3%), and pituitary (38.7%) were mostly involved. Cardiac (48.0% vs 0%, P=0.011) and vascular (52.0% vs 10%, P=0.031) involvements in ECD patients were more frequently than those in mixed LCH and ECD patients (Table 1). BRAFV600E mutations were detected in 64.8% ECD patients and 87.5% mixed LCH and ECD patients. BRAFV600E mutations correlated with more involved organs (6 vs 4, P=0.03), lung (77.4% vs 53.8%, P=0.033) and pleural involvement (56.6% vs 19.2%, P=0.002) compared to BRAFWT patients. The median number of mutated genes was 1 (range 0-8). Other MAPK and PI3K-Akt signal pathways gene mutations included MAP2K1 (4.7%), MAP3K1, PIK3CD, PIK3CA, ERBB3 and ERBB4 (1.5%, respectively). First-line treatments in ECD patients mainly included IFN-a (70.7%), BRAF inhibitors (14.6%), cytarabine ± IFN-a (4%), and steroids. The overall response rate was 79.3% with IFN-a, 90.7% with BRAF inhibitors, and 75% with cytarabine ± IFN-a. No response was observed in patients treated with steroids or observation. The median follow-up period was 38 months (range 1-174 months). 12 (14.1%) patients died during follow-up. The cause of death was associated with ECD or mixed LCH and ECD in 11 (91.7%) patients and AML in one patient. The median OS was not reached, and the estimated 5-year OS was 84.7%. Right atrial pseudotumor (HR, 4.419; 95% CI, 1.161-16.83; P=0.029) and pancreatic involvement (HR, 5.806; 95% CI, 1.069-31.539, P=0.042) were significantly correlated with worse OS. 38 (44.7%) patients had disease progression during follow-up. The median PFS was 54 months, and the estimated 5-year PFS was 45.3%. Pleural (HR, 2.987;95%CI, 1.190-6.187; P=0.018) and CNS involvement (HR, 2.714;95%CI, 1.190-6.187; P=0.018) were significantly predictors for poor PFS. BRAF status, number of mutations, and co-existence of LCH were not prognostic factors for survival. Summary/Conclusion: We revealed the clinical spectrum of ECD and mixed LCH and ECD patients, confirmed the effectiveness of IFN-a and BRAF inhibitors, and clarified the prognostic value of pancreatic involvement, atrial pseudotumor, CNS, and pleural involvement with worse survival. image: Table.1Keywords: Interferon-alpha, Prognostic factor, Kinase inhibitor, Langerhans Cell Histiocytosis